Core-shell lipid-polymer nanoparticles as a promising ocular drug delivery system to treat glaucoma

Nowadays, tremendous researches have been focused on the core-shell lipid-polymer nanoparticles (LPNs) due to the advantages of both liposomes and polymer nanoparticles. In this work, LPNs were applied to encapsulate brinzolamide (Brz-LPNs) for achieving sustained drug release, improving drug corneal permeation and enhancing drug topical therapeutic effect. The structure of Brz-LPNs was composed of poly(lactic-co-glycolic) acid (PLGA) nanocore which encapsulated Brz (Brz-NPs) and lipid shell around the core. Brz-LPNs were prepared by a modified thin-film dispersion method. With the parameters optimization of Brz-LPNs, optimal Brz-LPNs showed an average particle size of 151.23 +/- 1.64 nm with a high encapsulation efficiency (EE) of 86.7% +/- 2.28%. The core-shell structure of Brz-LPNs were confirmed by transmission electronic microscopy (TEM). Fourier transformed infrared spectra (FTIR) analysis proved that Brz was successfully entrapped into Brz-LPNs. Brz-LPNs exhibited obvious sustained release of Brz, compared with AZOPT (R) and Brz-LPs. Furthermore, the corneal accumulative permeability of Brz-LPNs significantly increased compared to the commercial available formulation (AZOPT (R)) in vitro. Moreover, Brz-LPNs (1 mg/mL Brz) showed a more sustained and effective intraocular pressure (IOP) reduction than Brz-LPs (1 mg/mL) and AZOPT (R) (10 mg/mL Brz) in vivo. In conclusion, Brz-LPNs, as promising ocular drug delivery systems, are well worth developing in the future for glaucoma treatment. (C) 2019 Chinese Chemical Society and Institute of Materia Medica, Chinese Academy of Medical Sciences. Published by Elsevier B.V. All rights reserved.